PROJECT SUMMARY Pulmonary nontuberculous mycobacterial (NTM) disease due to Mycobacterium avium complex (MAC) is an increasingly common, rare disease. MAC are environmental pathogens present in the soil and water that can cause chronic, debilitating pulmonary disease in predominately older patients with underlying lung disease. There are two distinct phenotypes, more commonly nodular disease associated with bronchiectasis and less commonly cavitary disease with underlying chronic obstructive pulmonary disease. Treatment consists of 3-5 off-label antibiotics for 18-24 months. Pulmonary MAC is difficult to eradicate, and relapse or reinfection from the environment is common. While microbiologic response is frequently achieved, the ability of this outcome measure to reflect how the patient feels, functions, or survives is poorly understood. In this application, we will expand our prior work with NTM patients and patient advocate stakeholders that identified the development of meaningful PRO measures and measuring treatment response using health-related quality of life (HRQoL) as top research priorities. Our proposed work uses a mixed methods approach and leverages our regional NTM referral clinic and recently initiated prospective randomized clinical trial of 2-drug vs. 3-drug therapy for pulmonary MAC (MAC2v3 trial). Dr. Kevin Winthrop is the principal investigator and OHSU serves as the coordinating center for the MAC2v3 trial. Recruiting from the NTM clinic, we will first conduct qualitative evaluation of whether the NTM Module missed any characteristic NTM symptoms in non- bronchiectatic patients (Aim 1a). We will further validate the NTM Module in treated patients in the MAC2v3 trial. MAC2v3 patients have nodular-bronchiectatic MAC (Aim 1b). PROs are collected at 5 time points (baseline, 1, 3, 6, and 12 months), and include HRQoL and symptoms (QOL-Bronchiectasis and NTM Module), and symptoms/toxicity (PRO-CTCAE, selected 40 items). We will describe longitudinal patterns of HRQoL and toxicity in treated patients, and further evaluate the relationship between toxicity and HRQoL over time (Aims 2a and 2b). Last, to evaluate feasibility for incorporating PROs in clinical practice (Aim 3) we will conduct focus groups with patients and survey clinicians to select the most relevant PROs for clinical care. In the pilot implementation aim we will incorporate a brief pre-visit electronic PRO survey in Dr. Winthrop's NTM clinic, evaluating the feasibility and acceptability of PROs in clinical practice and describe changes in care/management after pilot implementation. We will complete Aim 1a during Year 1, Aim 1b in Year 2, Aims 2a and 2b in Years 3- 4, and Aim 3 in Year 3. We anticipate that our work will produce a validated, NTM-disease specific PRO and evidence to support integration into clinical practice. This work will lay the foundation for future implementation and outcomes research of PROs for NTM patients, thus facilitating improved patient care for a complex, chronic disease.